Both wild-type and temperature-sensitive mutants of Rous sarcoma virus will be used to transform inbred Lewis rat embryo fibroblasts of known sex. The transformed cells will be characterized for virus rescue and several in vitro tests of transformation. Revertants will be selected, from a wild-type RSV-transformed line exhibiting a high rescue frequency, using EMS mutagenesis and various selective procedures. We hope to isolate cell mutants in functions required for expression of the tranformed phenotype. Tests for in vivo properties of malignancy, especially invasiveness and metastasis, will be developed using a chicken embryo chorioallantoic membrane model and a rat model. Transformed clones having high and low rates of metastasis and invasion will be selected by in vivo procedures. Several types of differentiated cells isolated from chicken embryos will be transformed by temperature-sensitive mutants of Rous sarcoma virus and compared for changes in expression of same functions and transformed cell properties. Yolk sac myeloblast cultures will be used to isolate non-producer clones of avian myeloblastosis virus. The clones will be employed to study the defectiveness of AMV and to isolate temperature sensitive mutants. Elaphe virus, a C-type virus isolated from the corn snake, will be investigated to determine its oncogenic potential and in vitro assays for the virus will be developed. Heterologous host systems involving homeotherms and poikilotherms will be developed using RSV, Elaphe virus and various reptilian and avian cells.